Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo investigate the characteristics of injury deaths and its disease burden in Taizhou City from 2009 to 2022, and to provide a basis for the prevention and control of injury. MethodsBased on the injury death surveillance data of Taizhou City from 2009 to 2022, the age-specific and sex-specific mortality rates, as well as the standardized mortality rates after adjusting China’s standardized population age of residents in Taizhou City were calculated. The crude mortality rate, standardized mortality rate, average years of life lost(AYLL), potential years of life lost (PYLL) and potential years of life lost rate (PYLLR) were calculated using Excel 2013 software. Joinpoint 4.2 software was used to estimate the annual percentage change (APC) and analyze the trends of injury mortality and PYLLR from 2009 to 2022. ResultsFrom 2009 to 2022, the standardized mortality rate of injuries in Taizhou City showed a decreasing trend (APC=-4.876%, P<0.001), with a mortality rate of 64.38/100 000 and a standardized mortality rate of 66.68/100 000. There was a statistically significant difference in injury deaths by genders (χ²=7 520.153, P<0.001). From 2009 to 2022, the PYLL and AYLL caused by injuries in Taizhou City were 587 518 person years and 21.91 years, respectively, with a PYLLR of 7.72%. The PYLLR of injuries showed a decreasing trend (APC=-7.454%, P<0.001), in addition, the PYLLR in urban(APC=-7.123%), rural areas (APC=-10.193%), males (APC=-7.595%) and females (APC=-7.046%) all showed a decreasing trend, all differences were statistically significant(all P<0.001). The top five causes of injury deaths leading to PYLL were traffic accident, drowning, accidental fall, suicide and accidental poisoning. ConclusionIn the last decade, injury has been a major cause leading to premature death among residents in Taizhou, with a higher mortality rate in males than that in females, and different injury characteristics caused by different types of injuries. It is necessary to take targeted injury prevention and intervention measures for different key population groups to effectively reduce the disease burden caused by injury deaths.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

Objective:To explore the medication law for threatened irritability in ancient gynecological monographs based on data mining.Methods:Based on Zhong Hua Yi Dian (5th edition), Chinese Medicine Resource Network and the paper version of ancient books, the representative gynecological monographs from the pre-Qin to the Qing Dynasty were selected to retrieve the prescriptions for the treatment of fetal irritability and establish a database. Excel 2019, IBM SPSS Modeler 18.0 and IBM SPSS Statistics 26.0 software were used to perform frequency statistics, association rule analysis and clustering analysis on the data of Chinese materia medica, analyze the core drug groups, and explore the medication laws. Results:A total of 151 prescriptions were included, including 7 kinds of TCM syndrome types, involving 111 kinds of Chinese materia medica. The most commonly used Chinese materia medica were Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Chuanxiong Rhizoma, and Paeoniae Radix Alba, etc. The efficacy categories were mainly tonic, heat-clearing, blood-activating and stasis-resolving; the medicinal properties were mainly warm and neutral; the tastes were mainly sweet and pungent; the main meridians were spleen, lung, liver and kidney meridians. 17 commonly used TCM combinations were obtained by association rule analysis, and five core TCM combinations were obtained by clustering analysis.Conclusions:In the treatment of threatened irritability, ancient doctors used the method of tonifying kidney and invigorating spleen, tonifying qi and nourishing blood, clearing heat and preventing miscarriage flexibly. The core drugs were mainly Angelicae Sinensis Radix, which was mostly modified on the basic prescriptions such as Siwu Decoction and Jiaoai Decoction.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

ObjectiveTo analyze the mortality rate and the changing trends of injury in Taizhou City from 2009 to 2022, so as to provide a reference for developing injury intervention strategies. MethodsSurveillance data on injury deaths of the registered residents in Taizhou from 2009 to 2022 were used, and descriptive statistics and χ² test were employed to analyze the mortality rates and differences by age group, gender, and region. Joinpoint regression analysis was used to analyze the trends and calculate the annual percentage change(APC). ResultsFrom 2009 to 2022, a total of 53 707 injury deaths were recorded in Taizhou, with a mortality rate of 64.38/10⁵ and a standardized mortality rate of 66.68/10⁵. The injury mortality rate showed a decreasing trend (APC=-1.30%, P<0.05). The top five causes of death were accidental falls, traffic accidents, drowning, suicide, and accidental poisoning, all showing a decreasing trend (APC=-3.30%, -7.65%, -2.77%, -5.78%, and -7.82%, respectively, all P <0.05). The leading causes of death for those under 15 years old, 15‒64 years old, and 65 years old and above were drowning, traffic accidents, and accidental falls, respectively. There was no statistical difference in the mortality rate between urban and rural areas (χ²=3.81, P=0.05), but there was a statistical difference between genders (χ²=7 520.15, P<0.01). ConclusionIn recent years, injury deaths among the residents in Taizhou have been decreasing. Efforts should be made to strengthen the prevention and control of injuries such as drowning in children, traffic accidents in middle-aged and young people, and accidental falls in the elderly.

Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.